Abstract: Objective: To establish an animal model of immune-mediated motoneuron injury. Methods: Adult male albino outbred Hartley guinea pigs were inoculated with bovine spinal cord anterior horn homogenized in phosphate-buffered saline (PBS) and suspended into emulsion in Freund's complete adjuvant. The injections were intra / subcutaneous over the back of each animal. Animals were examined every day during the experimental period. EMG examinations were carried out regularly. Samples were taken for histological and serological anti-spinal anterior horn antibody examinations. Results: 17/19 Guinea pigs immunized with bovine spinal cord anterior horn homogenate manifested limb and/or neck weakness and muscle atrophy. Electromyographic examination indicated denervation and motor unit potentials with high amplitude and wide time limit were observed. Pathologically, changes in different degree were found in pyramidal cells of the motor cortex and myelinated fibers in the cerebral peduncle. Loss and degeneration of motor neurons and gliosis were observed in spinal cord cervical and lumbar enlargement. The titer of antibodies to spinal cord anterior horn of guinea pig elevated in the immunized group, and IgG depositions were observed in anterior horn motoneurons. Conclusions: This study successfully established an animal model of immune-mediated motor neuron injury.